The prognostic value of circulating tumor DNA in patients with melanoma: A systematic review and meta-analysis.

BACKGROUND: Circulating tumor DNA (ctDNA) has been investigated as a potential prognostic biomarker to evaluate the therapeutic efficacy and disease progression in melanoma patients, yet results remain inconclusive. The purpose of this study was to illustrate the prognostic value of ctDNA in melanoma. OBJECTIVES: To describe the clinical prognostic value of ctDNA for melanoma patients. METHODS: Searched for eligible articles from Pubmed, Web of Science and Embase. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ctDNA at baseline or during treatment and overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 9 articles were obtained, involving 617 melanoma patients. The pooled HRs revealed that compared with baseline undetectable ctDNA patients, detectable ctDNA was highly correlated with poor OS (HR 2.91, 95% CI: 2.22-3.82; p < 0.001) and PFS (HR 2.75, 95% CI: 1.98-3.83; p < 0.001). A meta-analysis of these adjusted HRs was performed and confirmed that ctDNA collected at baseline was associated with poorer OS/PFS (OS: HR 3.00, 95% CI 2.19-4.11, p < 0.001/PFS: HR 2.68, 95% CI 1.77-4.06, p < 0.001). During treatment, a significant association was shown between ctDNA and poorer OS/PFS (OS: HR 6.26, 95% CI 2.48-15.80, p < 0.001; PFS: HR 4.93, 95% CI 2.36-10.33, p < 0.001). CONCLUSION: Investigation and application of ctDNA will improve "liquid biopsy" and play a role in early prediction, monitoring disease progression and precise adjusting treatment strategies in melanoma patients.

[Efficacy comparison between laparoscopy and open surgery in the treatment of gastric gastrointestinal stromal tumors larger than 2 cm using multicenter propensity score matching method].

Objective: To compare the efficacy between laparoscopy and open surgery for gastric gastrointestinal stromal tumor (GIST) larger than 2 cm. Methods: A multicenter retrospective cohort study was performed. Inclusion criteria: long diameter of primary gastric GIST > 2 cm; undergoing laparoscopy or open surgery; diagnosis confirmed by postoperative pathology without distant metastasis; without preoperative targeted therapy. Clinicopathological data of 857 gastric GIST patients, including 320 in PLA General Hospital, 284 in Shanghai Renji Hospital, 175 in Wuhan Union Hospital and 78 in Tianjin Cancer Hospital, from January 2010 to May 2017 were retrospectively collected. There were 418 males and 439 females, mainly aged between 50 and 70 years old. Among 857 patients, 413 were in the laparoscopy group and 444 in the open group. The nearest neighbor matching of propensity score matching method was conducted with 1:1 matching based on tumor location and size between laparoscopy and open group to obtain samples of covariate equilibrium, and the caliper value was 0.04. The t test, χ(2) test and Wilcoxon rank test were used to compare short-term efficacy, and the Kaplan-Meier curve and log rank test were applied to compare long-term outcomes between the two groups. Results: After propensity score matching, laparoscopy group and open group both enrolled 293 cases. The baseline data, including age, gender, tumor location, tumor long diameter, NIH classification, etc. were not significantly different between the two groups (all P>0.05). Compared with the open group, the laparoscopy group had less intraoperative blood loss [<100 ml: 2.9% (155/293) vs. 36.2% (106/293), Z=-12.857, P<0.001], shorter time to postoperative feeding [(4.0±0.2) days vs. (5.3±0.9) days, t=1.505, P=0.003] and to the removal of drainage tube [(4.8±1.0) days vs. (6.5±1.0) days, t=1.847, P=0.008], and shorter postoperative hospital stay [(8.6±0.3) days vs. (10.5±0.3) days, t=4.235, P<0.001]. Subgroups analysis according to anatomical location: (1) Gastric cardia and pylorus: there were no statistically significant differences in perioperative parameters between the two groups (all P>0.05). (2) Stomach base: feeding time after surgery [(4.0±0.2) days vs. (4.5±0.2) days, t=0.512, P=0.038], drainage tube removal time [(5.1±0.4) days vs. (6.4±0.6) days, t=0.517, P=0.044], postoperative hospital stay [(8.0±0.5) days vs. (11.1±0.9) days, t=0.500, P=0.002] were all significantly shorter in the laparoscopy group as compared to the open group, while the differences in other perioperative parameters were not statistically significant (all P>0.05). (3) Lesser curvature of the stomach: the laparoscopy group had less intraoperative blood loss [<100 ml ratio: 58.1% (43/74) vs. 33.7% (25/74), Z=7.632, P=0.034], shorter gastric tube removal time [(2.7±0.2) days vs. (3.2±0.3) days, t=0.503, P=0.007], earlier postoperative passage of gas [(2.8±0.1) days vs. (3.4±0.2) days, t=0.532, P=0.030], earlier postoperative feeding [(3.6±0.2) days vs. (4.3±0.2) days, t=0.508, P=0.020], shorter drainage tube removal time [(4.2±0.4) days vs. (5.7±0.5) days, t=0.508, P=0.020] and postoperative hospital stay [(8.3±0.6) days vs. (10.7±0.3) days, t=0.502, P=0.006] as compared to the open group. (4) Great curvature of the stomach: the laparoscopy group presented less intraoperative blood loss [<100 ml ratio: 52.7% (39/74) vs. 36.5% (27/74), Z=7.681, P=0.032], earlier gastric tube removal [(2.6±0.2) days vs. (3.6±0.2) days, t=0.501, P=0.001], earlier postoperative passage of gas [(2.7±0.2) days vs. (3.4±0.2) days, t=0.501, P=0.016], earlier postoperative feeding [(3.6±0.2) days vs. (4.7±0.2) days, t=0.500, P=0.001], shorter drainage tube removal time [(4.0±0.5) days to (5.9±0.4) days, t=0.508, P=0.002] and postoperative hospital stay [(7.5±0.3) days to (9.5±0.1) days, t=0.500, P=0.001] than the open group. Subgroup analysis according to tumor size: (1) Tumor long diameter 2.0-5.0 cm: the laparoscopy group had earlier passage of gas [(2.9±0.1) days vs. (3.5±0.1) days, t=0.500, P=0.001], earlier postoperative feeding [(4.5±0.1) days vs. (5.0±0.2) days, t=0.501, P=0.013], shorter drainage tube removal time [(4.8±0.3) days vs. (6.0±0.3) days, t=0.511, P=0.008] and postoperative hospital stay [(8.1±0.4) days to (10.1±0.3) days, t=0.513, P=0.001] than the open group. (2) Tumor long diameter 5.1-10.0 cm: in the laparoscopic group, postoperative feeding time [(4.0±0.2) days vs. (4.7±0.2) days, t=0.506, P=0.015], drainage tube removal time [(4.6±0.4) days vs. (6.4±0.5)) days, t=0.501, P=0.004], postoperative hospital stay [(8.2±0.3) days vs. (10.9±0.6) days, t=0.500, P=0.001] were all shorter than those in the open group. No intraoperative and postoperative complications were observed in each group. The 5-year recurrence-free survival rates of the laparoscopy group and the open group were 95.4% and 91.6%, respectively (P=0.734), and the 5-year overall survival rates were 93.8% and 90.8% (P=0.691), respectively, and the differences were not statistically significant. Conclusions: In experienced medical centers, laparoscopic surgery for gastric GIST larger than 2 cm is safe and feasible, and can achieve comparable efficacy with open surgery. For gastric GISTs which do not locate in the greater curvature and the anterior wall of the stomach, and whose long diameter is ≤5 cm, laparoscopic surgery does not increase the risk of recurrence and metastasis, and can accelerate postoperative recovery.

Association of UBASH3A gene polymorphism and atopic dermatitis in the Chinese Han population.

Genome-wide association studies have revealed a large number of genetic-risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases share susceptibility loci. Recent evidence has demonstrated that UBASH3A gene was associated with multiple autoimmune diseases. The aim of this study was to explore the association between UBASH3A single-nucleotide polymorphisms (SNPs) and atopic dermatitis (AD) in a Chinese Han population. In total, three UBASH3A SNPs (rs11203203, rs3788013 and rs1893592) were genotyped using TaqMan genotyping assays in a Chinese Han population (1012 cases and 1362 controls). Among these SNPs, we selected the SNP rs1893592 with association values of P<5 × 10-2 for AD in the TaqMan genotyping assay data for further replication in the independent Chinese replication samples (1080 cases and 1367 controls) using a Sequenom MassARRAY system. We combined the association results in two stages using meta-analysis. We found that rs1893592 in UBASH3A showed association with AD (P=1.29 × 10-3, odds ratio=1.16). These results showed that UBASH3A gene SNP is associated with susceptibility to AD. Further fine mapping and functional studies will be required to identify true causal variant in the UBASH3A gene and its exact role in the pathogenesis of AD.

Multiple variants in 5q31.1 are associated with systemic lupus erythematosus susceptibility and subphenotypes in the Han Chinese population.

BACKGROUND: A previous study provided evidence for a genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi-ancestral cohorts, but failed to find significant evidence for an association in the Han Chinese population. OBJECTIVES: To explore the association between this locus and SLE using data from our previously published genome-wide association study (GWAS). METHODS: Single-nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31.1) were selected as candidate independent associations from a large-scale study in a Han Chinese population consisting of 1047 cases and 1205 controls. Subsequently, 3509 cases and 8246 controls were genotyped in two further replication studies. We then investigated the SNPs' associations with SLE subphenotypes and gene expression in peripheral blood mononuclear cells. RESULTS: Highly significant associations with SLE in the Han Chinese population were detected for SNPs rs7726414 and rs244689 by combining the genotype data from our previous GWAS and two independent replication cohorts. Further conditional analyses indicated that these two SNPs contribute to disease susceptibility independently. A significant association with SLE, age at diagnosis < 20 years, was found for rs7726414 (P = 0·001). The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased compared with those in healthy controls. CONCLUSIONS: This study found evidence for multiple associations with SLE in 5q31.1 at genome-wide levels of significance for the first time in a Han Chinese population, in a combined genotype dataset. These findings suggest that variants in the 5q31.1 locus not only provide novel insights into the genetic architecture of SLE, but also contribute to the complex subphenotypes of SLE.

Effect of atmospheric fine particles on epidermal growth factor receptor mRNA expression in mouse skin tissue.

We investigated the effect of atmospheric fine particles on epidermal growth factor receptor (Egfr) mRNA expression in mouse skin tissue and explored the effect of atmospheric fine particles on skin aging. Forty female BALB/c mice were randomly divided into four groups (each comprising 10 mice) as follows: a saline control group and low-, medium-, and high-dose atmospheric fine particle groups (1.6, 8.0, and 40.0 mg/kg, respectively) (fine particles were defined as those with a diameter of £2.5 mm, i.e., PM2.5). Each dose group was exposed to intratracheal instillation for 3 days. Twenty-four hours after the last exposure, real-time quantitative polymerase chain reaction was used to detect the expression of Egfr mRNA in the skin tissue of each mouse. The expression levels of Egfr mRNA in the medium- and high-dose PM2.5 groups were significantly higher (P < 0.05) than that in the control group, and were positively correlated with the dose. Medium and high concentrations of PM2.5 can induce the expression of Egfr mRNA and promote skin aging.

Genetic variants of the genes encoding zinc finger protein 313 and interleukin-13 confer a risk for psoriasis in a Chinese Uygur population.

BACKGROUND: Recent work using genome­wide association studies (GWAS) in Chinese Han and white populations have discovered several novel psoriasis susceptibility genes. AIM: To examine whether the risk loci for psoriasis identified in previous GWAS in a white population are also associated with psoriasis in a Chinese Uygur population in Xinjiang. METHODS: Genotyping analysis of eight single-nucleotide polymorphisms (SNPs) associated with psoriasis was performed for 539 patients with psoriasis and 749 controls, all of Chinese Uygur descent, using a commercial assay. RESULTS: Two SNPs had an association with psoriasis in this Chinese Uygur population: SNP rs495337 in the gene encoding for zinc finger protein 313 (P < 0.001; OR = 0.80) and SNP rs20541 of the gene encoding for interleukin-13 (P < 0.001; OR = 0.82). In subgroup analyses, the two SNPs were significantly associated (P < 0.05) with type I psoriasis, Rs495337 showed statistically difference between positive family history of psoriasis patients and controls whereas rs20541 might preferentially associated with negative family history psoriasis patients. Interestingly, using multifactor dimensionality reduction, a significant two-locus interaction was seen between rs495337 and rs20541, with a crossvalidation consistency of 4/5 and average balanced prediction (accuracy 55.5%, P < 0.001). CONCLUSIONS: ZNF313 and IL-13 are associated with risk for psoriasis in a Chinese Uygur population, and there is an effect of interaction between the two genes on this risk.

Azimuthal reorientation of pentacene upon 2D condensation.

We report a novel two-dimensional gas-solid phase transition of pentacene molecules on the Cu(110)-(2 × 1)O surface where the 2D condensation is accompanied by a reversible azimuthal rotation of the pentacene molecules. The change of the optical anisotropy associated with this reorientation allows us to explore the 2D condensation as a function of coverage and temperature by reflectance difference spectroscopy. As a result, the 2D heat of condensation of pentacene on Cu(110)-(2 × 1)O is determined to be 84 meV, which is more than one order of magnitude smaller than the respective value for 3D crystallization.

Optical probe for surface and subsurface defects induced by ion bombardment.

We demonstrate that reflectance difference spectroscopy (RDS) is sensitive to defects induced by ion bombardment, located either in the topmost layer or in the subsurface region. Most importantly, these two kinds of defects can be spectrally discriminated, since the corresponding signatures in the RD spectrum arise from perturbations of different types of electronic states: The defects in the topmost surface layer mainly lead to a quenching of the optical anisotropy related to surface states, whereas the subsurface defects strongly affect the optical anisotropy originating from transitions between surface-modified bulk electronic states. Consequently, RDS can be used to simultaneously monitor the defects in the topmost surface layer and in the subsurface region in-situ during ion bombardment and thermal annealing. [Formula: see text] Characteristic RD spectra and the corresponding STM images for a Cu(110) substrate before and after healing of the subsurface defects.

A single-nucleotide polymorphism rs4639966 in 11q23.3 is associated with clinical features of systemic lupus erythematosus in the Chinese population.

In our previous genome-wide association study (GWAS), we identified an association signal of the single-nucleotide polymorphism (SNP) rs4639966 (p = 1.25 × 10(-16), odds ratio [OR] = 1.29) within 11q23.3. The aim of this study was to investigate its relationship with disease subphenotypes, including renal nephritis, photosensitivity, antinuclear antibody (ANA), age at diagnosis, malar rash, discoid rash, immunological disorder, oral ulcer, hematological disorder, neurological disorder, serositis, arthritis and vasculitis. In this study, we used 4199 cases and 8255 controls from our previous GWAS to explore the association between 11q23.3 with subphenotypes of systemic lupus erythematosus (SLE). Data were analyzed with PLINK 1.07 software. Significant associations were found for the SNP rs4639966 of 11q23.3 with SLE of age at diagnosis <20 years (OR = 1.18, p = 0.0049), malar rash (OR = 1.13, p = 0.01) and vasculitis (OR = 1.17, p = 0.02). The study suggested that 11q23.3 might not only play important roles in the development of SLE, but also contribute to the complex phenotypes of SLE.

Genetic variant rs4982958 at 14q11.2 is associated with allergic rhinitis in a Chinese Han population running title: 14q11.2 is a susceptibility locus for allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is one of the most common diseases caused by the combined effects of intrinsic factors (susceptibility genes and immunological status) and the external environment. Analyses of ascendant family history of atopic disease suggest that AR and atopic dermatitis might share a similar genetic background. OBJECTIVE: To conduct a case-control study in a Chinese Han population to evaluate the potential influence of single nucleotide polymorphisms (SNPs) at FLG, 5q22.1, 11q13.5, 14q11.2 and 20q13.33 on AR. METHODS: Ten SNPs--rs11204971 and rs3126085 at FLG, rs10067777, rs7701890, rs13360927, and rs13361382 at 5q22.1, rs6010620 at 20q13.33, rs7936562 and rs7124842 at 11q13.5, and rs4982958 at 14q11.2 were genotyped in 363 cases and 668 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. RESULTS: The T allele of rs4982958 at 14q11.2 was observed to be significantly associated with AR (P = .002, OR = 0.73, P(Bonferront) = .02). Genotype-based association testing revealed that the recessive model might provide the best fit for rs4982958 (P(Bonferroni) = .01). In subphenotype analyses, the rs4982958 T allele was also significantly associated with persistent AR (P = .01) and more than 2 positive skin prick tests (P = .038). CONCLUSION: We identified a novel susceptibility locus 14q11.2 for AR that might bear candidate genes conferring susceptibility to AR and affecting disease phenotypes.

Growth and optical properties of Ag clusters deposited on poly(ethylene terephthalate).

The growth and concomitant evolution of the optical properties of Ag nano-clusters deposited on biaxially extruded poly(ethylene terephthalate) films is studied by reflectance difference spectroscopy. It is demonstrated by low energy ion scattering and simulated optical spectra that the clusters form a two-dimensional layer buried beneath the surface of the substrate. The experimental spectra are described by simulations in which different configurations of the host such as anisotropy, amorphization, and dilution are considered in an effective medium approach. The contribution of the anisotropic substrate is used to explain the resulting line shapes. We also discuss the role of the rate of change of the filling fraction with Ag coverage in the evolution of the spectra and the detection of the onset of coalescence by optical means.

Initial stage of crystalline rubrene thin film growth on mica (0 0 1).

We have studied the morphology and the spatially resolved photoluminescence of rubrene thin films at the early stage of crystallization. The initial growth proceeds via the formation of a wetting layer and the nucleation of islands with an amorphous structure. Crystallization starts when the amorphous islands coalesce and needle like crystalline fibers are formed in the gap between islands. The crystalline fibers then grow on top and in between the original amorphous islands leading to an "open network" of islands. The latter acts as the basis for the growth of semi-crystalline spherulites.

Comparisons of clinical features of HLA-DRB1*07 positive and negative vitiligo patients in Chinese Han population.

BACKGROUND: Human leucocyte antigen (HLA)-II alleles have been found to be associated with vitiligo in different populations, and several studies also suggested that HLA class II alleles/haplotypes were associated with a different type vitiligo. Of HLA class II alleles, DRB1*07 has consistently shown a positive association with vitiligo in Chinese Han population. OBJECTIVE: To further explore the relationship between DRB1*07 and vitiligo and to evaluate the DRB1*07 effect on the clinical features of vitiligo in Chinese Han population. METHODS: This study investigated DRB1*07 allele distribution in 1178 unrelated Chinese vitiligo patients and 1743 healthy controls using polymerase chain reaction/sequence specific primer method and observed clinical differences between DRB1*07 positive and DRB1*07 negative patients. RESULTS: The analysis of the 1178 cases and 1743 controls revealed a highly association between DRB1*07 allele and vitiligo [odds ratio (OR) = 1.97, P = 2.13 × 10(-17) ]. DRB1*07 positive patients had early disease onset (OR = 1.49, P = 0.001), higher frequency of family history (OR = 1.44, P = 0.006) compared with DRB1*07 negative patients. CONCLUSIONS: The DRB1*07 showed significant association with vitiligo in the study population. This study confirmed that DRB1*07 positive patients had some obvious clinical differences from DRB1*07 negative patients in the Chinese Han population.